The present invention relates to (A) the promotion of vascular growth of new capillaries in a spherical pool in a preselected area as close to the skin surface as possible within the human or animal body. The proximity of this newly formed spherical capillary pool (vascular pool) beneath the defatted thinned skin allows for bidirectional application of introduction of chemical agents (B). This allows for rapid and accurate transcutaneous absorption of any suitable medication (which term includes all drugs and other agents) into the circulation. The selection of appropriate highly charged chemical elements. For example, fluorides will accelerate the transcutaneous passage through the thinned skin directly into the circulation of the capillary pool without alteration or loss of bio-availability.
The capillary pool (C) may also be employed to detect electrochemical charges emitting from various blood elements circulating in the capillary pool to pass in reverse direction through the skin to an appropriate sensor overlying the capillary pool.
Broadly, three OBJECTS of this invention are:
A. Developing a new blood vessel capillary pool.
B. Transmitting chemical medications and other physical substances and elements directly into the bloodstream for controllable and predictable responses.
C. Transmitting immuno-biochemical information from the blood pool to sensors applied to the external surface of the skin thinned and defatted, as by acetone. The transmission of electrochemical signals from the blood elements in the circulation in reverse direction from the capillary pool through the thinned skin (opposite to conventional methods) to a sensor applied over the capillary pool. Biochemical and/or electrochemical sensors can be employed. The sensor therefore can directly read these signals from many chemical substances circulating in the blood. Thus, it is also possible to electrochemically detect oxygen, carbon dioxide, the pH of blood, and the percent saturation of oxygen.
Medications are administered orally, or injected directly into the vascular system, or absorbed into the vascular system transcutaneously. Introducing medications through oral administration is followed by absorption through the stomach and intestines. Some substances ingested orally are altered by the digestive system in or en route to the vascular system. Sometimes less than 50% of the substance is available in an effective form for absorption and treatment. Therefore, some substances are not suitable for oral administration, others are less effective when they reach the vascular system, thus decreasing the intended benefit at the target or organ for which the substance was intended.
The oral route for introducing medicines is often not preferred because of unfavorable side effects (for example, fluoride salts administered orally form hydrofluoric acid in the stomach, discomforting the patient). Needle puncture and other conventional entry techniques often do not provide continuous easy accessibility to the blood. Piercing the skin for long periods introduces the threat of bleeding, clotting and infection. Also, blood vessels may collapse or become blocked after extended use for introduction of medications.
Furthermore, the oral administration or subcutaneous injection require absorption time, during which the tissues and fluids can bind the medicine or alter its effectiveness.
Another current method for introducing medicine is by absorption through the skin. This method has limited application due to slow absorption rates in the skin surface. Also, tissue fluids bind or alter effectiveness before it is absorbed into the vascular system. Therefore, doses of a medicine otherwise administered must often be wastefully larger.
Accordingly, there has existed a definite need for a simple, efficient, safe, rapid and effective means of introducing substances into the vascular system and for avoiding problems associated with needle dislodgement.
Basic elements are known and employed in this new proposal:
In the prior art of transdermal passage of medications through the skin, the amount of absorption is relatively small and often uncontrollable.
Those transdermal medications react as they would by the intravenous route and are often highly variable. Yet, the chemical/medication reaction is unchanged. Many medications are partially insoluble and do not transmit well through the skin.
Conventional transdermal delivery is virtually useless for delivery of peptide drugs whose sizes are too big and too fat-insoluble to pass-through the fat layers of the skin and the underlying subcutaneous blood vessels.
Fortunately, now there exist many available (in their rapidly growing field) sensors that can function when introduced into the venous or arterial circulation. The newly developed capillary blood pool of this invention does not use an implanted indwelling blood sensor. The sensor is applied to the thinned skin surface over the capillary pool. Therein the sensors can transmit or receive information continuously for blood glucose or tissue fluid glucose concentration for controlling and/or treating, and transmit that data to an external receiver. These sensor devices are now available for a use with this invention to measure glucose, urea, antibiotics, and many other relevant chemical substances to transmit and receive, and interpret, and treat medical conditions with this information obtained from this capillary pool for individual patients (see
1. Velho, Froguel, Sternberg, Thevenot, Reach, "In vitro and In vivo Stability of Electrode Potentials In Needle-Type Glucose Sensors", Diabetes, vol. 38: 164-171, 1989. PA1 2. Bard, Faulkner, "Electrochemical methods", Fundamentals and Applications. New York, Wiley, 1980. PA1 3. Hitchman, "Measurement of Dissolved Oxygen", Geneva, Wiley/Orbisphere, 1978 PA1 4. Ives, Janz, "General and Theoretical Introduction!`, Reference Electrodes, Theory and Practice, New York Academic, 1961. PA1 5. Armour, Lucisano, McKean, Gough, "Application of Chronic intravascular Blood Glucose Sensor in Dogs", Diabetes, vol 39: 1519-1526, 1990. PA1 6. McKean, Gough, "A Telemetry-Instrumentation System for Chronically Implanted Glucose and Oxygen Sensors", IEEE Trans Biomed Eng 35: 52 6-32, 1988).
Another object of the invention is to improve and accelerate the absorption of substances and medications through the skin in minimal volume for short or long periods with much better control and predictability. Conventional transcutaneous absorption is relatively small and wherein the chemical reactions from the medication react as they would by the intravenous route but in much less degree, again, often uncontrollable. The major object and result of the capillary pool is that the chemical/medication reaction is unchanged so that the passage through the thinned skin does not alter the chemical reaction.
Transmitting accurate amounts of chemical elements and medications, and biological substances through the skin directly into the capillary blood circulation, and thence into the entire circulation almost immediately, the control of the amount of agents that are being transcutaneously introduced into the circulation, makes it possible to introduce oxygen, and other readily exchangeable gases, and chemical and physical agents, including antibiotics. Other therapeutic substances would permit the acceleration of absorption of substances to readily accessible circulation in minimal volume for short or long term periods, with small amounts of medication and with much higher control and more predictable results for long-term, continuous use.
This could also afford ready access if necessary to obtain blood samples from an easily accessible capillary pool for chemical determinations or other means for administering materials which may be life saving. This would avoid searching for conventional blood vessels particularly when patients may be in shock and have no discernible blood pressure. The capillary pool will always remain available. This would be much more effective than subcutaneous or intramuscular injections.
An equally important feature is to allow information to be obtained continuously from the capillary pool through the capillary wall and skin to an external sensor in close proximity positioned over the capillary pool. These sensors are functional by electrochemical transmission, but it has up to this time required direct insertion of a sensitive electrode into the bloodstream by needle or catheter implantation. This invention now permits the newly vascularized capillary pool to transmit that information directly through the skin onto a cutaneous sensor without implantation by conventional methods. This will allow the bloodstream to read directly onto an overlying sensor which can determine blood sugar for use in diabetes control; for sodium and potassium and other chemical elements which are often critically needed in the daily medical control of many patients. For example, the sensor signal of excess blood sugar can trigger the release of insulin through another capillary pool to control the blood sugar level. In reality it could serve as an electronic pancreas blood sugar regulation in diabetes. This signal can also be received telemetrically at a central receiving station in a hospital or medical building or even physician's offices which permit daily home care, or for alerting patients at their daily occupation. This opens a great opportunity for determining medical care of patients on a continuous basis while performing daily tasks or even at sleep or at rest.